Goodwin Kelly, Orbaugh Kristi, Duncan Kirsten, Stumpf Erica
From Massachusetts General Hospital, Boston, Massachusetts.
Community Hospital Oncology Physicians, Indianapolis, Indiana.
J Adv Pract Oncol. 2024 Sep 12:1-17. doi: 10.6004/jadpro.2024.15.8.16.
The V600E mutation aberrantly activates the mitogen-activated protein kinase (MAPK) pathway, subsequently resulting in uncontrolled cellular proliferation, survival, and dedifferentiation. Approximately 2% of patients with non-small cell lung cancer (NSCLC) have a V600E mutation. BRAF and MEK inhibitor combination therapy targets two kinases within the MAPK pathway. Encorafenib (Braftovi) and binimetinib (Mektovi) are potent oral inhibitors of BRAF and MEK, respectively. With the recent US Food and Drug Administration approval of encorafenib plus binimetinib, adult patients with V600E-mutated metastatic NSCLC have an additional treatment option. In the phase II PHAROS study, encorafenib plus binimetinib achieved the primary endpoint of objective response rate by independent review committee and exhibited a manageable safety profile in this patient population. This article provides an overview of the efficacy and safety of encorafenib plus binimetinib and uses a fictional patient case to illustrate the role of advanced practice providers in providing individualized patient care and identifying and managing adverse reactions.
V600E 突变异常激活丝裂原活化蛋白激酶(MAPK)通路,随后导致细胞不受控制地增殖、存活和去分化。非小细胞肺癌(NSCLC)患者中约 2% 存在 V600E 突变。BRAF 和 MEK 抑制剂联合疗法靶向 MAPK 通路中的两种激酶。恩考芬尼(Braftovi)和比美替尼(Mektovi)分别是 BRAF 和 MEK 的强效口服抑制剂。随着美国食品药品监督管理局最近批准恩考芬尼联合比美替尼,V600E 突变的转移性 NSCLC 成年患者有了额外的治疗选择。在 II 期 PHAROS 研究中,恩考芬尼联合比美替尼达到了独立审查委员会评估的客观缓解率这一主要终点,并且在该患者群体中显示出可管理的安全性。本文概述了恩考芬尼联合比美替尼的疗效和安全性,并通过一个虚构的患者病例来说明高级执业医师在提供个体化患者护理以及识别和管理不良反应方面的作用。